Serum amino acids, central monoamines, and hormones in drug-naive, drug-free, and neuroleptic-treated schizophrenic patients and healthy subjects

doi:10.1016/0165-1781(90)90003-N

Psychiatry Research

Volume 34, Issue 3, December 1990, Pages 243-257

https://doi.org/10.1016/0165-1781(90)90003-N Get rights and content

Abstract

Basal serum amino acids (including central monoamine precursors), central monoamines, and hormones were studied in schizophrenic patients (drug-naive, n = 20; drug-withdrawn for 3 or more days, n = 67; neuroleptic-treated, n = 23) and healthy subjects (n = 90) to answer the following questions: (1) Do neuroleptic-withdrawn and neuroleptic-naive patients differ on these serum measures? (2) What are the effects of neuroleptic treatment on these measures? (3) On which variables do drug-free and neuroleptic-treated patients differ? Because serum amino acid, central monoamine, and hormone levels were similar in drug-naive and drug-withdrawn patients, data from these groups (“drug-free”) were combined and compared to those of healthy subjects and neuroleptic-treated patients. Asparagine, citrulline, phenylalanine, and cysteine were higher, while tyrosine, tryptophan, and the ratio of tryptophan to competing amino acids were significantly lower in drug-free schizophrenic patients than in healthy subjects. Dopamine was increased, and melatonin and thyroid hormones were decreased in drug-free schizophrenic patients compared to healthy subjects. Norepinephrine, epinephrine, and prolactin were higher in neuroleptic-treated men compared to drug-free male patients or healthy men. These results are consistent with the hypothesis of dopaminergic overactivity in schizophrenia, which might be caused by altered amino acid precursor availability and could be related to the decrease in melatonin and reduction in thyroid hormone levels.

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Prolactin, CAR and morning cortisol blood concentrations in AN-FEP group in relation to HC group.
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Citation Excerpt :
Experiments have shown that genetically modified mice with artificially created BH4 deficiency showed dopamine deficiency in the brain, as well as behavioral abnormalities specific for an experimental model of schizophrenia (Leeming et al., 1976). BH4 is also a cofactor of nitric oxide synthase, which synthesizes nitric oxide (NO) from L-arginine (Rao et al., 1990). NO triggers a protein phosphorylation signaling cascade (Snyder and Ferris, 2000), which is a regulator of monoaminergic neurotransmission (Kiss, 2000), as well as of the glutamatergic system.
It was reported that the levels of tetrahydrobiopterin (BH4) are reduced in schizophrenia. However, mechanisms of BH4 deficiency in schizophrenia had not been studied precisely. Objective: the search of the association between BH4 deficiency in schizophrenia and a range of biochemical and clinical parameters for the evaluation of the possible mechanisms of BH4 loss and its role in the development of the symptoms. Methods: 93 patients with schizophrenia and 60 healthy volunteers were randomly selected and evaluated with a biochemical examination of BH4, folate, cobalamin (B12), homocysteine, C-reactive protein (CRP), reduced glutathione (GSH) levels in the blood serum.Patients underwent standardized psychopathological examination. Results: In patients, the levels of BH4 and folate were lower (p = 0.001 and p = 0.054, respectively), and the levels of homocysteine were higher (p = 0.012) compared to the control group. BH4 levels directly moderately correlated with folate (ρ = 0.43; p = 0.0029) and B12 levels (ρ = 0.43; p = 0.0020) and inversely moderately correlated with homocysteine levels (ρ = −0.54; p = 0.00015) in patients. Cluster analysis identified schizophrenia biotype characterized by a deficiency of BH4, folate, B12, and hyperhomocysteinemia. The clinical characteristics of this biotype were not specific. CRP and GSH were higher in patients compared to controls, but their association with serum BH4 was not confirmed.
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^☆: This article is part of the Dissertation of Bernd Strebel, Hohe Medizinische Fakultät der Universität Bonn. The results were presented at the Annual Meeting of the American College of Neuropsychopharmacology, December 1989, Maui, HI.

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Serum amino acids, central monoamines, and hormones in drug-naive, drug-free, and neuroleptic-treated schizophrenic patients and healthy subjects☆

Abstract

European Journal of Pharmacology

Biological Psychiatry

Psychiatry Research

Journal of Biological Chemistry

Progress in Neuro-Psychopharmacology

Psychiatry Research

Life Sciences

Psychoneuroendocrinology

Life Sciences

Biological Psychiatry

Workshop on schizophrenia, PET, and dopamine D2 receptors in the human neostriatum

Schizophrenia Bulletin

Biological correlates of suicidal behavior

Resting urinary catecholamine excretion in schizophrenics: Methodology and interpretation of results

Biological Psychiatry

Plasma amino acids in relation to cerebrospinal fluid monoamine metabolites in schizophrenic patients and healthy controls

British Journal of Psychiatry

The role of serotonin in schizophrenia

Schizophrenia Bulletin

Acute psychosis and plasma catecholamine metabolites

Archives of General Psychiatry

Novel double-isotope technique for enzymatic assay of catecholamines, permitting high precision, sensitivity and plasma sampling capacity

Clinical Science

Low serum prolactin and early relapse following neuroleptic withdrawal

American Journal of Psychiatry

Role of serine, glycine, and the tetrahydrofolic acid cycle in schizoaffective psychosis: A hypothesis relating porphyrin biosynthesis and transmethyl ation

Adrenergic receptors in depression: Effects of electroconvulsive therapy

British Journal of Psychiatry

A simple and sensitive radioreceptor assay for antischizophrenic drugs in blood

Nature

Plasma noradrenaline and clinical psychopathology in schizophrenia

Neuropsychobiology

A comparison of plasma homovanillic acid concentrations in schizophrenic patients and normal controls

Archives of General Psychiatry

Plasma homovanillic acid as a predictor of response to neuroleptics

Archives of General Psychiatry

Pharmacoendocrinology of schizophrenia

Increased whole blood serotonin concentrations in chronic schizophrenic patients

Archives of General Psychiatry

Report of the National Cholesterol Education Program Expert Panel on detection, evaluation and treatment of high blood cholesterol in adults

Archives of Internal Medicine

No D2 receptor increase in a PET study of schizophrenia

Archives of General Psychiatry

Neutral amino acids in the brain: Changes in response to food ingestion

Journal of Neurochemistry

Brain serotonin content: Psysiological regulation by plasma neutral amino acids

Science

Effect of age on thyroid hormone physiology and function

Geriatric Bioscience

Screening for aminoacidurias in psychiatric inpatients

Archives of General Psychiatry

Plasma drug and homovanillic acid levels in psychotic patients receiving neuroleptics

Biological Psychiatry